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FDA Expands Approved Use of Imbruvica (Ibrutinib) for CLL

New clinical data support drug’s traditional approval

July 29, 2014

The FDA has expanded the approved use of Imbruvica (ibrutinib, Pharmacyclics/Janssen Biotech) to treat patients with chronic lymphocytic leukemia (CLL) who carry a deletion in chromosome 17 (17p deletion), which is associated with poor responses to standard treatment for CLL. Imbruvica had received a “breakthrough therapy” designation for this use.

The FDA also approved new labeling to reflect that the clinical benefit of Imbruvica in treating CLL has been verified.

In February 2014, Imbruvica received accelerated approval to treat CLL based on its effect on the overall response rate. New clinical trial results examining progression-free survival and overall survival have confirmed the drug’s clinical benefit.

A type of non-Hodgkin lymphoma, CLL is a rare disease of the blood and bone marrow that usually gets worse slowly over time, causing a gradual increase in B lymphocytes. The National Cancer Institute estimates that 15,720 Americans will be diagnosed and 4,600 will die from CLL in 2014. Imbruvica works by blocking the enzyme that allows cancer cells to grow and divide.

Imbruvica is the fourth drug approved to treat CLL that received a “breakthrough therapy” designation. The other treatments are Gazyva (obinutuzumab, Genentech) in November 2013; Arzerra (ofatumumab, GlaxoSmithKline) in April 2014; and Zydelig (idelalisib, Gilead) in July 2014. The application for accelerated approval of Imbruvica to treat CLL did not receive a “breakthrough therapy” designation.

The FDA’s approval actions for Imbruvica were based on a clinical study of 391 previously treated participants, 127 of whom had CLL with the 17p deletion. The subjects were randomly assigned to receive ibrutinib or ofatumumab until disease progression or side effects became intolerable.

The study was stopped early for efficacy after a pre-planned interim analysis showed that ibrutinib-treated participants experienced a 78% reduction in the risk of disease progression or death (i.e., progression-free survival). The results also showed a 57% reduction in the risk of death (i.e., overall survival) in subjects treated with ibrutinib. Of the 127 participants who had CLL with the 17p deletion, those treated with ibrutinib experienced a 75% reduction in the risk of disease progression or death.

The most common side effects associated with ibrutinib included thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory-tract infection, rash, nausea, and fever.

The new use for Imbruvica was approved more than 2 months ahead of the product’s prescription drug user fee goal date of October 7, 2014 — the date the FDA was scheduled to complete its review of the drug application.

Imbruvica also received accelerated approval in November 2013 for the treatment of patients with mantle-cell lymphoma who had received at least one prior therapy. Clinical studies to verify and describe the clinical benefit of Imbruvica in mantle-cell lymphoma are ongoing.

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